Experimental and Therapeutic Medicine
·
2018
·Vol. 16
·期 2
·925-930
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IF 1.41
Wen‑Jie Li,You‑Wen Lian,Quan‑Sheng Guan,Ning Li,Wen‑Jun Liang,Wen‑Xin Liu,Yong‑Bin Huang,Yi Cheng,Hui Luo
Liver‑targeted drug delivery improves the efficacy of anti‑liver cancer agents and reduces systemic toxicity by limiting the bioavailability of these drugs to within tumors. Liver targeting reagents with galactose residues, which selectively combine to asialoglyco protein receptors, have previously been used to improve liposome‑encapsulated drug accumulation within liver cells. They lead to a reduction in liver cancer cell growth and have been used to cure certain hepatic diseases. In the present study, curcumol, which is the primary active component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated‑liposomes to enhance its anti‑liver cancer efficacy. Galactosylated‑liposomes and normal liposomes were labeled with propidium iodide. Galactosylated‑liposomes with increasing concentrations of galactosylated‑stearate (Gal‑s) had a notably increased level of uptake in HepG2 cells (hepatoblastoma) compared with SGC‑7901 (gastric cancer) and A549 (non‑small cell lung cancer) cells. When the percentage of Gal‑s reached 20%, liposome uptake plateaued. In the in vitro anti‑liver cancer experiment, the anti‑liver cancer efficacy of galactosylated‑curcumol‑liposomes increased significantly more compared with normal curcumol liposomes and free curcumol as indicated by cell survival rate and lactate dehydrogenase release rate. Collectively, these results demonstrate that galactosylated‑liposomes are able to enhance the in vitro liver‑targeting effect and anti‑liver cancer efficacy of curcumol.
研究领域:
药理学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2022
·Vol. 36
·期 12
·e22665
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IF 5.834
Yang Zheng,Tiejian Zhao,Jiaru Wang,Ruizhu Jiang,Jinbiao Huang,Weimin Li,Jiahui Wang
To explore the effect of curcumol on autophagy and ferroptosis of hepatic stellate cells, and to clarify the molecular mechanism of its anti-hepatic fibrosis. In the present study, we report that curcumol promotes the death of activated HSCs and reduces the deposition of extracellular matrix. Interestingly, curcumol treatment can trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Curcumol promotes HSC autophagy, which may be the key mechanism for its induction of ferroptosis. It is worth noting that the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a key molecular mechanism. NCOA4 mediates the release of iron ions and induces the occurrence of ferroptosis. Overall, curcumol promotes autophagy in hepatic stellate cells, mediates the degradation of NCOA4 and FTH1 complexes, releases iron ions, leads to iron overload, and induces ferroptosis, which may be an important mechanism for its anti-hepatic fibrosis effect.
研究领域:
药理学
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细胞生物学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2014
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IF 0.968
Ping Guo,Yue-Wu Wang,Bi-Xia Weng,Xiao-Kun Li,Shu-Lin Yang,Fa-Qing Ye
Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by 1H, 13C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure–activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.
研究领域:
药理学
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化学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Jiaojiao Chen,Shaoxia Wang,Huiyuan Zhang,Huixiang Li,Fei Wang,Yinglin Wang,Quan Zhao
Chemotherapy proves to be a successful method in treating primary breast cancer. Ironically, some commonly used chemotherapeutics may promote lung metastasis by increasing the activity of activating transcription factor 3 (ATF3). Thus, it is necessary to inhibit tumor metastasis while improving the anti-tumor effect of anti-cancer drugs. Herein, using curcumol (CUR) that possesses both anti-tumor and anti-metastasis activities as a model drug, we designed the nanogels based on temperature-responsive self-assembly and glutathione-triggered disassembly to address the abovementioned conflicts. Briefly, the copolymers (H-SS-P) were synthesized by coupling poly (N-isopropylacrylamide) onto hyaluronic acid (HA) via a disulfide bond-containing linker cystamine dihydrochloride . Copolymers could self-assemble into regular spherical nanogels at 37 °C with a 40-nm particle size for PNIPAAm's thermosensitivity. Hydrophobic CUR could be automatically entrapped into the core of nanogels. The H-SS-P@CUR nanogels could release drugs quickly upon exposure to the reductive tumor microenvironment . The superior efficacy of H-SS-P@CUR on inhibiting tumor growth was validated through assays both in vivo and in vitro . Moreover, nanogels may better down-regulate the expression of ATF3 protein by enhancing the cell uptake and tumor targeting of CUR, thereby significantly improving the anti-metastasis effect of CUR. This work not only proposed a novel strategy to simplify the preparation process of nanogels but also achieved effective drug delivery with enhanced anti-cancer and anti-metastasis effects.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 18
·2938-2947
·
IF 5.047
Jing Wang,Yonghong Song,Mingxun Zhang,Zhensheng Wu,Yun-Jun Xu,Jun Lin,Daishun Ling,Youjing Sheng,Yang Lu,Qiang Wu
Combination chemotherapy has improved the life quality of patients suffering from ovarian cancer; however, drug resistance and late relapse lead to a high mortality rate. As a bioactive component in zedoary oil, curcumol has been widely used against gynecological tumors in the clinic. However, the bioavailability of curcumol is limited by its indissolubility in water. The design of nano-formulas is promising to improve traditional drugs in the clinic, which is beneficial for the treatment of malignant diseases, especially cancer. Herein, a liposomal curcumol nanocomposite was prepared for the theranostics of human primary ovarian cancer cells from solid tumor tissue in patients. In this uniform nanocomposite, curcumol and a frequently used magnetic resonance contrast agent, gadopentetate dimeglumine (Gd-DTPA), were effectively wrapped in the hydrophobic lipid bilayer and aqueous cavity of the liposome, respectively. Parallel assessments of the anti-tumor ability and mechanism of liposomal curcumol were performed on both SKOV3 and human primary ovarian cancer cells, and the results indicated the induction of apoptosis in ovarian cancer cells by this curcumol nanocomposite via the endoplasmic reticulum pathway. Liposomal curcumol has been further confirmed to inhibit the growth of SKOV3 human ovarian cancer xenografts on tumor-bearing nude mice. Moreover, this gadolinium-based liposomal curcumol nanocomposite exhibited excellent T1-weighted magnetic resonance imaging (MRI) capability for the efficient detection of xenograft ovarian cancer, leading to a novel multifunctional therapeutic agent.
研究领域:
药学
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肿瘤学
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纳米技术
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医学影像
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产品关联
DOI
高影响因子
ONCOLOGY REPORTS
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2017
·Vol. 38
·期 6
·3583-3591
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IF 2.662
Shilei Zang,Qiling Tang,Fangrui Dong,Huan Liu,Lili Li,Fang Guo,Xuediao Pan,Haorong Lin,Weibin Zeng,Zhaoxu Cai,Qibin Zhong,Ning Zang,Linquan Zang
Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining followed by fluorescence activated cell sorting (FACS) analysis demonstrated that the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species (ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803 cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
European Journal of Integrative Medicine
·
2023
·
IF 2.5
Xuelin Duan,Tiejian Zhao,Jiaru Wang,Jiahui Wang,Yang Zheng
Introduction : Curcuma is used as an herbal remedy for the treatment of chronic liver diseases, and its main active ingredient is curcumol. This study explored the molecular mechanism of curcumol in regulating glutamine metabolism. Methods : The current investigation used lipopolysaccharide(LPS) to activate hepatic stellate cells (HSCs) and then analyzed the effects of curcumol on glutamine metabolism and cell proliferation. The effects of curcumol on glutaminase 1 (GLS1), senescence-related proteins, and extracellular matrix (ECM) expression were examined by western blotting and reverse transcription-quantitative polymerase chain reaction(RT-PCR). The effect of curcumol on the cell cycle was detected by flow cytometry. Furthermore, after overexpression of GLS1, we observed the effects of curcumol on glutamine metabolism, the expression of related molecules, and the cell cycle. Results : Curcumol significantly inhibited cell proliferation, glutamine metabolism, and GLS1 and ECM expression, and also significantly promoted cell senescence. With GLS1 overexpression, the inhibitory effects of curcumol on glutamine metabolism and on promoting cell senescence were rescued. Conclusion : Curcumol targets GLS1, inhibits glutamine metabolism, and induces senescence in HSCs. GLS1 may be an important target for the pharmacological effects of curcumol.
研究领域:
药理学
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细胞生物学
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肝病学
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Yang Zheng,Jiahui Wang,Jiaru Wang,Ruizhu Jiang,Tiejian Zhao
Objective Liver fibrosis is a reversible pathological process, and its prevention and treatment hold great significance for patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and serum metabolomics to explore the mechanism of curcumol’s effect on liver fibrosis in mice. The results clarified the relationship between the gut microbiota and metabolites in the process of liver fibrosis. Materials and methods In this study, we randomly divided mice into a control group, a model group, and a curcumol treatment group to analyze the pathological changes in the liver tissue as well as the activities of the toll-like receptor 4 (TLR4)/nuclear factory kappa B (NF-κB) signaling pathway and inflammatory factors, such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-8. The gut microbiota were analyzed by 16 S rRNA sequencing, and serum metabolites were examined by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Results Molecular biological testing found that curcumol could significantly improve the pathological changes of the liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol’s antihepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2. Conclusions When liver fibrosis occurs, the intestinal flora and metabolic network are altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby reducing liver inflammation.
研究领域:
药理学
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肝病学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Jingjing Yang,Hai Zhu,Wenhao Liang,Xingzeng Zhao,Min Yin,Xu Feng,Bi Wang
Phytophthora capsici is an infamously soil-borne pathogen that poses a serious threat to agricultural production. Curcumol is a natural plant-derived sesquiterpene lactone, whose antimicrobial effect against plant pathogens remains unclear. In this study, curcumol exhibited pronounced antifungal activity against a diverse range of plant pathogens, particularly against plant pathogenic oomycetes, which including P. capsici , Phytophthora infestans , Phytophthora parasitica , and Phytophthora sojae . The median effective concentration values of curcumol against P. capsici for spore germination and mycelial growth were 4.75 and 2.11 μg mL −1 , respectively. After treatment with curcumol, mycelia of P. capsici exhibited morphological and ultrastructual defects, which included swelling, hyperbranching, dissolution of plasma membrane, and loss of organelles. In addition, curcumol effectively inhibited the synthesis of phosphatidylcholine (PC), a primary component of cell membrane, by downregulating the expression levels of genes participated in PC synthesis such as Phospholipid N-methyltransferase and Cholinephosphotransferase . This inhibition decreased the accumulation of PC and phospholipids within the cell, thereby increasing the cell membrane permeability and damaging its integrity. In the in vivo antifungal tests, curcumol reduced the disease incidence of P. capsici on tomato leaves as well as pepper seedlings. The systemicity tests further validated the strong phloem and xylem mobility of curcumol in both upward and downward directions. Taken together, these results indicated that curcumol could effectively combat diseases caused by P. capsici and had the potential for development into a novel fungicide for P. capsici management.
研究领域:
植物病理学
·
真菌学
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农业科学
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药理学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Jingyi Wu,Qianqian Wang,Zhuang Deng,Shuo Zhang,Zhen Jiao
A novel drug nanocarrier with a magnetic core and an organic framework (MOF) shell was constructed by in situ growth of a three-dimensional network ZIF-8 on the surface of carboxy-functionalized Fe3O4. The resulting drug delivery system (DDS) showed strong superparamagnetism, boasting exceptional magnetization saturation at 11.15 emu/g, an impressive magnetocaloric effect of a temperature rise of 12.9 °C within 6 minutes at 20 A, and a significant T2-weighted MR image property. The drug encapsulation ability was investigated by loading a model drug namely curcumaol (CUR) onto the nanocarriers through supercritical solution impregnation (SSI) technology. The resulting Fe3O4@ZIF-8-CUR achieved a maximum loading content of 2.2 wt%, displaying 3.4 times higher than that using ethanol impregnation process. As expected, a continuous drug release behavior of Fe3O4@ZIF-8-CUR was observed. This study presents a state-of-the-art methodology of designing biocompatible DDSs with magnetic responsiveness for advanced drug delivery applications.
研究领域:
材料科学
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yang Zheng,Jiaru Wang,Tiejian Zhao,Lei Wang,Jiahui Wang
Ethnopharmacological relevance Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease . Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol. Aim To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis . Materials and methods We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, AKT, eNOS , CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group. Results The results of the MTT test found that the proliferation rate of each group was higher. The results of the molecular biology tests found that curcumol inhibited the activity of the VEGF/AKT/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group. Conclusions Curcumol inhibits the activity of the VEGF/AKT/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.
研究领域:
药理学
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分子生物学
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肝病学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Shanshan Jia,Pin Guo,Junhua Lu,Xujun Huang,Laming Deng,Yan Jin,Lanyan Zhao,Xiaofang Fan
Background Curcumol exhibits anti-inflammatory effect, but its effect on chronic asthma lacked research. Therefore, this study explored the role of curcumol in asthma.Methods A chronic asthmatic mice model was established by ovalbumin induction. After treatment with curcumol, airway resistance in mice was detected by forced oscillation technique. The histopathological features of airway tissues, pulmonary inflammation, and inflammation cell recruitment in the bronchoalveolar lavage fluid (BALF) of mice were detected by hematoxylin-eosin staining. Collagen deposition in the airways of mice was examined by Masson staining. The secretion of ovalbumin-IgE, IL-4, IL-5, IL-13 in mouse serum and VEGFA secretion in BALF were analyzed by ELISA. Finally, the expressions of β-catenin, Wnt5a, VEGFA, TGF-β1, Fibronectin, and MMP-9 in mice lung tissues were determined by Western blot or immunohistochemical.Results Curcumol attenuated airway hyperresponsiveness, airway remodeling, and pulmonary inflammation in chronic asthmatic mice. Curcumol relieved collagen deposition in airway tissues, inflammation cell recruitment in BALF, and reduced the up-regulation of serum ovalbumin-IgE, IL-4, IL-5, and IL-13 and BALF VEGFA in chronic asthmatic mice. In addition, curcumol attenuated the up-regulated expressions of β-catenin, Wnt5a, VEGFA, TGF-β1, Fibronectin, and MMP-9 in the lung tissues of chronic asthmatic mice, but curcumol treatment did not show such effects on healthy mice.Conclusion Our findings revealed that curcumol could ameliorate lung inflammation and airway remodeling by inhibiting the abnormal activation of the Wnt/β-catenin pathway in chronic asthmatic mice, indicating that curcumol could be used as a novel anti-asthma drug for basic and clinical research.
研究领域:
药理学
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免疫学
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呼吸医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）